title: Human endothelial lecitin-like oxLDL receptor-1 (LOX-1) expression is not associated with impairment of endothelium-dependent vasoreactivity in conduit vessels.
abstract: The cellular uptake of oxidized low density lipoprotein (LDL) is mediated through the oxidized LDL receptor-1, LOX-1. We investigated whether circulating factors link LOX-1 expression in endothelial cells and impaired endothelium-dependent vasoreactivity (EDVR) as functional indicator of atherogenesis. EDVR was measured as flow-mediated dilation (FMD) of the brachial artery in 27 patients with a known history of cardiovascular disease. Human umbilical vein endothelial cells (HUVEC) were incubated with bradykinin or prostacyclin in the presence of tumour necrosis factor-alpha (TNF-α) or with serum of each patient for four hours. Total mRNA and protein extracts were analysed for LOX-1 and eNOS expression relative to the expression in medium-treated cells and corrected for GAPDH expression.
  
  
  RESULTS
  Prostacyclin and bradykinin did not modulate LOX-1 basal expression but were able to prevent significantly the up-regulation of LOX-1 expression by TNF-α, in HUVEC in vitro. Impaired EDVR was associated significantly with reduced endothelial nitric oxide synthase (eNOS) protein expression in HUVEC (r=0.788, P<0.001), diabetes (P=0.024), and smoking status (yes/no, P=0.047). In contrast, no such association was established with LOX-1 mRNA (r=0.292, P=0.138) or with LOX-1 protein expression in HUVEC (r=0.201, P=0.312).
  
  
  CONCLUSIONS
  Using a combination of in vitro experiments with in vivo measurements, we found no evidence that endothelial LOX-1 expression and EDVR mediated through circulating factors were associated.
authors.affiliation: Department of Internal Medicine B, University Medicine Greifswald, Germany. martin.landsberger@gmx.net.
authors.forename: E
authors.initials: E
authors.lastname: Wetterau
authors.forename: S-S
authors.initials: SS
authors.lastname: Stecher
authors.forename: B
authors.initials: B
authors.lastname: Wolff
authors.forename: S
authors.initials: S
authors.lastname: Khouri
authors.forename: A
authors.initials: A
authors.lastname: Staudt
authors.forename: S B
authors.initials: SB
authors.lastname: Felix
authors.forename: M
authors.initials: M
authors.lastname: Landsberger
mesh_terms: D000368:Aged; D001916:Brachial Artery / Q000502:physiology; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000378:metabolism* / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012039:Regional Blood Flow; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C495137:OLR1 protein, human; D012333:RNA, Messenger; D051127:Scavenger Receptors, Class E; D014409:Tumor Necrosis Factor-alpha; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III